title: Abnormal neutrophil chemotactic activity in children with congenital insensitivity to pain with anhidrosis (CIPA): the role of nerve growth factor.
abstract: A 1926-ins-T mutation in the TrkA gene encoding the tyrosine kinase receptor for nerve growth factor (NGF) was previously documented in patients with congenital insensitivity to pain with anhidrosis (CIPA). These patients suffer from skin lacerations which often evolve into deep tissue infections. Abnormality in neutrophil functions may explain this high rate of severe infections. In this study we show that chemotaxis was significantly (P<0.001) suppressed in patients' neutrophils, compared to healthy controls. Although NGF alone did not exert a chemotactic effect, its presence enhanced both migration toward fMLP and phosphorylation of MAP kinases (ERK and JNK) in neutrophils from healthy controls, but not in neutrophils from CIPA patients. The significantly impaired chemotactic activity of neutrophils from a CIPA patient, which has been attributed to the molecular defect in the TrkA receptor, may contribute to the high rate of infection.
authors.affiliation: Department of Pediatrics, Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84101, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Beigelman
authors.forename: Jacov
authors.initials: J
authors.lastname: Levy
authors.forename: Nurit
authors.initials: N
authors.lastname: Hadad
authors.forename: Vered
authors.initials: V
authors.lastname: Pinsk
authors.forename: Alon
authors.initials: A
authors.lastname: Haim
authors.forename: Yariv
authors.initials: Y
authors.lastname: Fruchtman
authors.forename: Rachel
authors.initials: R
authors.lastname: Levy
mesh_terms: D000293:Adolescent; D000328:Adult; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D007007:Hypohidrosis / Q000150:complications*; D007223:Infant; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D000699:Pain Insensitivity, Congenital / Q000150:complications* / Q000276:immunology / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D018925:Chemokines; D020932:Nerve Growth Factor; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4